CRISPR-Cas9 Safely Used in Cancer Treatment

By Mike Howie

Researchers have recently shown that CRISPR-Cas9 gene editing could be a useful tool for cancer treatment. In a recent study published in Science, three patients were treated with edited immune cells to encouraging results: once implanted, the cells were stable for at least nine months in all three patients, and none of the patients developed dangerous side effects.

Each of the patients who participated in the study had advanced cancers that were not responding to traditional therapies — two had advanced refractory myeloma and one had metastatic sarcoma. To treat the patients, the researchers removed and edited about 100 million immune system cells from each.

The researchers used CRISPR to make four edits to the cells: First, they removed the protein PD-1, which cancer uses to stop immune cells from attacking. Next, they made two edits to remove receptors from the surface of the cells. Finally, they added a new synthetic T-cell receptor that guides the immune cells toward a particular cancer antigen. These edited cells were then injected back into the patients in the hope that they would more effectively seek and destroy cancer cells.

As the new cells went to work, the researchers closely monitored their patients. Blood tests showed that the cells were thriving in all three — none of their bodies rejected the cells — and further testing of the retrieved cells in the lab showed that they still killed cancer cells up to nine months after infusion. In comparison, similar chimeric antigen receptor (CAR) T-cell therapies persisted for only about two months. The blood tests also showed, however, that the CRISPR editing process left a few unintended DNA changes. Further monitoring showed that these changes faded in time.

The sarcoma patient saw the best response — their tumor initially shrank — but the study was never meant to determine effectiveness. Rather, it was designed to test if the treatment is safe and feasible, and in that regard the study was a success.

This is just a first step in developing a new cancer treatment, and these results are, of course, quite preliminary. But, according to Carl June, a cancer researcher at the University of Pennsylvania (UPenn) and a senior author of the study, it uncovered two new and important facts: “First, we can successfully perform multiple edits with precision during manufacturing, with the resulting cells surviving longer in the human body than any previously published data have shown. Second, thus far, these cells have shown a sustained ability to attack and kill tumors.”

With such promising results, the researchers are planning another trial that will help push their research even further. That trial will eventually involve 18 participants with sarcoma, melanoma, or myeloma.

According to Laurie Zoloth, a bioethicist at the University of Chicago who helped the National Institutes of Health review the study, this is the right approach. “Doing it slowly, doing it with a small group of patients and making no grandiose claims is exactly what you’d like to see in a trial like this,” she said.

The study’s success opens new possibilities for both cancer and disease research, and it helps to illustrate the powerful potential of CRISPR-Cas9. Edward Stadtmauer, MD, an oncology professor at UPenn and the study’s principal investigator, commented, “We hope this is the beginning of the next generation of engineering cells to help many different diseases and many different tumors.”